Two medicines, side by side
Amitriptyline vs fluoxetine
Amitriptyline and fluoxetine are both labeled for depression. Drugs@FDA records approvals of amitriptyline since 1961 and of fluoxetine since 1987. Pharmacies paid $0.03 per amitriptyline HCl 10 mg tablet and $0.0519 per fluoxetine HCl 40 mg capsule (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. In FDA's classes, amitriptyline is a tricyclic antidepressant and fluoxetine a serotonin reuptake inhibitor.
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026); the fluoxetine FDA label on DailyMed (effective January 8, 2026).
Highlights of the amitriptyline record
Amitriptyline (Elavil) · label of September 8, 2026
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Used for
From the label: indicationsFor the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
On the market
- Earliest approval on file
- April 7, 1961
- Generic labelers
- 34 labelers
- Pharmacy cost
- $0.03 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 2
Highlights of the fluoxetine record
Fluoxetine (Prozac) · label of January 8, 2026
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions ( 5.1 )].
Used for
From the label: indicationsPROZAC ® is indicated for the treatment of: Acute and maintenance treatment of Major Depressive Disorder [see Clinical Studies ( 14.1 )]. Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [see Clinical Studies ( 14.2 )]. […]
On the market
- Earliest approval on file
- December 29, 1987
- Generic labelers
- 58 labelers
- Pharmacy cost
- $0.0519 per capsule
Supply and safety
- Shortage
- No current entry
- Recalls
- 9
Source: FDA drug labels via openFDA (Amitriptyline label of September 8, 2026, Fluoxetine label of January 8, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do amitriptyline and fluoxetine differ on the record?
In FDA's classes, amitriptyline is a tricyclic antidepressant and fluoxetine a serotonin reuptake inhibitor.
How each works, in its label's words: Amitriptyline, “It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.”; Fluoxetine, “Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.”
Both labels carry a boxed warning; the records quote them.
Generics: amitriptyline since 1976; fluoxetine since 2001 (Drugs@FDA).
| Amitriptyline | Fluoxetine | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety, Bipolar disorder |
| Pharmacologic class | Tricyclic Antidepressant | Serotonin Reuptake Inhibitor |
| How it works (label) | in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system. | Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. |
| Half-life (label) | n/a | Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days. |
| Earliest approval on file (Drugs@FDA) | April 7, 1961 | December 29, 1987 |
| First generic approved | November 16, 1976 | August 2, 2001 |
| Generic labelers (NDC) | 34 labelers | 58 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.03 per tablet (Amitriptyline HCl 10 mg tablet) | $0.0519 per capsule (Fluoxetine HCl 40 mg capsule) |
| 12-month price change | -19% | -20% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 2 | 9 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 17,441 | 131,827 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
Do their labels mention each other?
Amitriptyline label, drug interactionsWhile all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
Source: FDA drug labels via openFDA
What do the labels say about using others of their kind?
Amitriptyline label, warningsIf concomitant use of amitriptyline hydrochloride with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
Fluoxetine label, warnings and precautionsSerotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents.
Source: FDA drug labels via openFDA
What next?
- Alternatives to amitriptyline
- every medicine labeled for the same conditions